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Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study

BACKGROUND: Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational a...

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Autores principales: Kaiser, Hannah, Kvist-Hansen, Amanda, Becker, Christine, Wang, Xing, McCauley, Benjamin D, Krakauer, Martin, Gørtz, Peter Michael, Henningsen, Kristoffer Mads Aaris, Zachariae, Claus, Skov, Lone, Hansen, Peter Riis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JMIR Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512189/
https://www.ncbi.nlm.nih.gov/pubmed/34581684
http://dx.doi.org/10.2196/28669
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author Kaiser, Hannah
Kvist-Hansen, Amanda
Becker, Christine
Wang, Xing
McCauley, Benjamin D
Krakauer, Martin
Gørtz, Peter Michael
Henningsen, Kristoffer Mads Aaris
Zachariae, Claus
Skov, Lone
Hansen, Peter Riis
author_facet Kaiser, Hannah
Kvist-Hansen, Amanda
Becker, Christine
Wang, Xing
McCauley, Benjamin D
Krakauer, Martin
Gørtz, Peter Michael
Henningsen, Kristoffer Mads Aaris
Zachariae, Claus
Skov, Lone
Hansen, Peter Riis
author_sort Kaiser, Hannah
collection PubMed
description BACKGROUND: Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational analysis techniques offer new opportunities to improve the understanding of disease connections. OBJECTIVE: We aim to characterize the complexity of cardiovascular risk in patients with psoriasis by integrating deep phenotypic data with systems biology techniques to perform comprehensive multiomic analyses and construct network models of the two interacting diseases. METHODS: The study aims to include 120 adult patients with psoriasis (60 with prior atherosclerotic CVD and 60 without CVD). Half of the patients are already receiving systemic antipsoriatic treatment. All patients complete a questionnaire, and a medical interview is conducted to collect medical history and information on, for example, socioeconomics, mental health, diet, and physical exercise. Participants are examined clinically with assessment of the Psoriasis Area and Severity Index and undergo imaging by transthoracic echocardiography, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT), and carotid artery ultrasonography. Skin swabs are collected for analysis of microbiome metagenomics; skin biopsies and blood samples are collected for transcriptomic profiling by RNA sequencing; skin biopsies are collected for immunohistochemistry; plasma samples are collected for analyses of proteomics, lipidomics, and metabolomics; blood samples are collected for high-dimensional mass cytometry; and feces samples are collected for gut microbiome metagenomics. Bioinformatics and systems biology techniques are utilized to analyze the multiomic data and to integrate data into a network model of CVD in patients with psoriasis. RESULTS: Recruitment was completed in September 2020. Preliminary results of (18)F-FDG-PET/CT data have recently been published, where vascular inflammation was reduced in the ascending aorta (P=.046) and aortic arch (P=.04) in patients treated with statins and was positively associated with inflammation in the visceral adipose tissue (P<.001), subcutaneous adipose tissue (P=.007), pericardial adipose tissue (P<.001), spleen (P=.001), and bone marrow (P<.001). CONCLUSIONS: This systems biology approach with integration of multiomics and clinical data in patients with psoriasis with or without CVD is likely to provide novel insights into the biological mechanisms underlying these diseases and their interplay that can impact future treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28669
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spelling pubmed-85121892021-11-02 Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study Kaiser, Hannah Kvist-Hansen, Amanda Becker, Christine Wang, Xing McCauley, Benjamin D Krakauer, Martin Gørtz, Peter Michael Henningsen, Kristoffer Mads Aaris Zachariae, Claus Skov, Lone Hansen, Peter Riis JMIR Res Protoc Protocol BACKGROUND: Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational analysis techniques offer new opportunities to improve the understanding of disease connections. OBJECTIVE: We aim to characterize the complexity of cardiovascular risk in patients with psoriasis by integrating deep phenotypic data with systems biology techniques to perform comprehensive multiomic analyses and construct network models of the two interacting diseases. METHODS: The study aims to include 120 adult patients with psoriasis (60 with prior atherosclerotic CVD and 60 without CVD). Half of the patients are already receiving systemic antipsoriatic treatment. All patients complete a questionnaire, and a medical interview is conducted to collect medical history and information on, for example, socioeconomics, mental health, diet, and physical exercise. Participants are examined clinically with assessment of the Psoriasis Area and Severity Index and undergo imaging by transthoracic echocardiography, (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT), and carotid artery ultrasonography. Skin swabs are collected for analysis of microbiome metagenomics; skin biopsies and blood samples are collected for transcriptomic profiling by RNA sequencing; skin biopsies are collected for immunohistochemistry; plasma samples are collected for analyses of proteomics, lipidomics, and metabolomics; blood samples are collected for high-dimensional mass cytometry; and feces samples are collected for gut microbiome metagenomics. Bioinformatics and systems biology techniques are utilized to analyze the multiomic data and to integrate data into a network model of CVD in patients with psoriasis. RESULTS: Recruitment was completed in September 2020. Preliminary results of (18)F-FDG-PET/CT data have recently been published, where vascular inflammation was reduced in the ascending aorta (P=.046) and aortic arch (P=.04) in patients treated with statins and was positively associated with inflammation in the visceral adipose tissue (P<.001), subcutaneous adipose tissue (P=.007), pericardial adipose tissue (P<.001), spleen (P=.001), and bone marrow (P<.001). CONCLUSIONS: This systems biology approach with integration of multiomics and clinical data in patients with psoriasis with or without CVD is likely to provide novel insights into the biological mechanisms underlying these diseases and their interplay that can impact future treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28669 JMIR Publications 2021-09-28 /pmc/articles/PMC8512189/ /pubmed/34581684 http://dx.doi.org/10.2196/28669 Text en ©Hannah Kaiser, Amanda Kvist-Hansen, Christine Becker, Xing Wang, Benjamin D McCauley, Martin Krakauer, Peter Michael Gørtz, Kristoffer Mads Aaris Henningsen, Claus Zachariae, Lone Skov, Peter Riis Hansen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 28.09.2021. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included.
spellingShingle Protocol
Kaiser, Hannah
Kvist-Hansen, Amanda
Becker, Christine
Wang, Xing
McCauley, Benjamin D
Krakauer, Martin
Gørtz, Peter Michael
Henningsen, Kristoffer Mads Aaris
Zachariae, Claus
Skov, Lone
Hansen, Peter Riis
Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title_full Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title_fullStr Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title_full_unstemmed Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title_short Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study
title_sort multiscale biology of cardiovascular risk in psoriasis: protocol for a case-control study
topic Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512189/
https://www.ncbi.nlm.nih.gov/pubmed/34581684
http://dx.doi.org/10.2196/28669
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